A third patient death potentially tied to Eisai and Biogen’s Alzheimer’s disease drug lecanemab has been reported in a phase 3 extension study, according to a report from Science.
The latest death was attributed to brain swelling and bleeding, as well as seizures. The patient was a 79-year-old Florida woman who was participating in the extension portion of the phase 3 trial, according to Science.
Eisai confirmed the death in an email statement to Fierce Biotech Thursday morning but declined to provide specific details on the patient citing a commitment to privacy for patients who participate in clinical studies. The company also said that information coming from other sources outside of scientific papers “may not have all the information necessary to make an accurate conclusion.”
“As a general comment on the unfortunate occurrences of participants in clinical trials who pass away—any evaluation of a death or deaths must consider the age of the population and their other medical conditions, as well as the length of the study,” an Eisai spokesperson said in the statement. “The rates of deaths and causes of deaths that we are observing in the lecanemab studies are consistent with those expected in people this age, as well as what was observed in our long-term Aricept experience.”
Aricept is Eisai’s first Alzheimer’s medicine that was approved in the U.S. in 1997. It was followed up by Aduhelm, which was developed with Biogen and approved last year under the accelerated review pathway only to struggle once on the market.
The company also said in its statement that the rate of deaths in the lecanemab study were similar to the placebo group and does not suggest an increase in deaths overall.
The previous two deaths were attributed to a common side effect of this class of drugs called amyloid-related imaging abnormalities, or ARIA, which are abnormalities that show up in MRI imaging and can signal bleeding in the brain or swelling.
These deaths have cast a shadow over the success of lecanemab in the late-stage trial, a rarity for an Alzheimer’s med. Eisai announced in September that the therapy slowed cognitive decline in the phase 3 Clarity AD trial, meeting the main endpoint and providing the data needed to support a potential regulatory nod.
Speaking to criticism in the Science article that the company should have revealed the third death at the recent Clinical Trials on Alzheimer’s Disease (CTAD) conference, the spokesperson said all safety information and serious adverse events are collected as quickly as possible and reported to the FDA consistent with requirements.
“Eisai strongly believes in a rigorous scientific approach of publishing information in peer-reviewed scientific journals or scientific congresses. To that end, the CTAD presentation included an analysis of the safety information, particularly reports of ARIA, known to us at the time,” the statement said.
The company does not believe that this latest death can be attributed to ARIA and it had not been reported as such at the time of the CTAD presentation.
“Eisai has been working diligently to learn more about this case. Unfortunately, as of yet, the investigator has not been provided access to the hospital records,” the company said.
Moreover, the extension study was not the focus of the CTAD presentation, therefore this latest death was not included in the presentation, the company added. The extension portion of the trial is ongoing and adverse event data has not been verified.
From adverse event data that has been recorded from the phase 3 so far, the rate of serious adverse events due to ARIA was seven patients out of 989, or 0.8%. All of these cases resolved. Eisai has also recorded 25 cases of symptomatic brain swelling, known as ARIA-E, and of those, three were considered clinically severe.
Eisai told Fierce Biotech last month in an interview that ARIA is a known side effect of this class of medicine and one that patients and doctors will have to discuss before starting treatment.
The trial win gave a much-needed boost to Alzheimer’s drug development research, which this year notched two high-profile failures from Genentech’s candidates, gantenerumab and crenezumab.
Ending its statement, Eisai once again made the case for lecanemab’s approval, promising to work with the FDA to make clear the risk of ARIA and infusion reactions on the drug’s future label.
“As with all therapies, patients and their families should discuss the benefits and risks in relation to their condition and medical history with their healthcare provider, prior to initiating treatment,” the company said.